The purpose of the proposed research project will be to study the molecular basis for cell-cell communication via gap junctions, and to study the biological role of gap junctional communication during embryonic development and tissue differentiation. The present proposal contains an integrated effort utilizing protein chemical, ultrastructural, immunological, biophysical, and recombinant DNA approaches. The specific aims include studies on: characterization of isolated gap junctions; generation of gap junction antibodies; reconstitution of gap junction channels; synthesis and biogenesis of gap junctions in vitro and in vivo; biological role of communication in embryonic development; and relationship between communication and gene expression during cell differentiation. We will continue the initial observations on fibrinogen that have resulted from our current studies on gap junctions. Thus far, these studies have provided the basis for identifying fibrinogen as a major component of the extracellular matrix (ECM) of a variety of tissues. The specific aims include studying: the characteristics of ECM fibrinogen; figrinogen gene expression in various tissues; biosynthesis of ECM fibrinogen in vitro and in vivo; developmental expression of fibrinogen in embryos; and the biological role of fibrinogen during embryonic development.